Human Behaviors Related to the Expectation of Pain

May 12, 2023 updated by: Johns Hopkins University

Physiological Studies in Healthy Subjects, Chronic Pain Patients and in Patients Undergoing Neurosurgical Procedures of Human Forebrain Mechanisms Mediating Somatic Sensation, Motor Control and Neurological Disorders

The conditioned expectation of pain is an important aspect of pain-related disability produced by environments and stimuli associated with a painful injury on the job, although the neuroscience of this expectation is unclear. We will develop and use novel objective methods for measurement of expectation and threat related attention. The results of this study may lead to testable hypotheses regarding the psychological basis of the fear of pain, threat and task related attention. We will also use these results, and development of novel autonomic and ratings metrics for state and trait anxiety as well as threat and task related attention which could be used as an instrumented test for diagnosis and management of PTSD and anxiety disorders. .

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The conditioned expectation or fear of pain often results in disability produced by stimuli related to a painful injury on the job, although there are questions about attentional and anxiety related expectation. Conditioned expectation in humans can be produced by a protocol that consists of a train of two visual conditioning stimuli, one of which is paired (CS+) with a painful laser pulse unconditioned stimulus (US), while the other is not. This protocol will be used to study the expectation of pain in this study, and its relationship to task and threat related attention measured by eye position and to anxiety, task directed sustained attention, and scalp EEG metrics. These results may also be used in an instrumented test for the diagnosis and management of PTSD and anxiety disorders.

EEG studies may clarify the relationship of unpleasantness (valence) and the ability of stimuli to command attention (salience) of the conditioned and unconditioned stimuli which which are significant but under studied aspects of the fear of the pain. Studies of scalp EEG activation and functional connectivity will be used to estimate global properties of the forebrain networks involved in the fear of pain, as well as the valence and the salience) of the conditioned and unconditioned stimuli.

Activations are measured by the proportion of electrodes over a quadrant or lobe of the scalp a significant ratio of electrical power following an event over baseline (event related spectral perturbation, ERSP). Functional connectivity will be measured by causal interactions following an event over baseline. The approach of this protocol is that causal interactions are based upon causal influences by an approach based upon the concept of linear predictability. Briefly, a signal Y is said to exert an influence upon signal X when the predication error of the X is reduced by adding the past information of Y (causal interaction). The signals from any two quadrants or lobes will be analyzed by event related causality to determine the magnitude and direction of causal interactions between the two to determine fear and pain related directed interactions related to aversive conditioning.

Our Preliminary Data shows EEG activations in global distributed forebrain networks for the expectation of pain are consistent with the evidence of studies of anatomic projections and functional MRI (fMRI) signals. These models including our Preliminary Data from intracranial recordings identify structures in the medial temporal lobe (amygdala and hippocampus) which are involved in expectation of pain, while EEG suggests global activations related to valence and salience of conditioned and unconditioned stimuli. The premise of this study is that novel autonomic and eye position metrics will measure state and trait anxiety as well as threat and task related attention to parse out the experience and anticipation of pain.

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Fred A Lenz, MD PhD
  • Phone Number: 4109606817
  • Email: flenz1@jhmi.edu

Study Contact Backup

  • Name: Nathan E Crone, MD
  • Phone Number: 410 955 6772
  • Email: ncrone@jhmi.edu

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287-7713
        • Recruiting
        • Hopkins Epilepsy Monitoring Unit, Zayhed 12.
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 88 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Man or woman between 18 and 80 years of age.
  • Fluent speaker of English.
  • Undergoing seizure monitoring at Hopkins Hospital through intracranial electrodes.
  • Possess ability to understand study procedures and comply with them for the entire length of the study;
  • Women of childbearing age must use pharmacological contraception (oral or patch) for the duration of the study follow-up.

Exclusion Criteria:

  • Inability or unwillingness of individual to give written informed consent. Presence of any neurological disease other than epilepsy which is unstable or is not optimally treated.
  • Presence of a significant abnormality on routine neuropsychological testing.
  • Presence of any medical or psychiatric disease which is unstable or is not optimally treated.

Presence of an abnormal MRI scan except for Normal variants or Medial Temporal Sclerosis (altered pathology and MRI signal in temporal lobe).

  • Women who are pregnant or women of childbearing capacity who may become pregnant (i.e. not using contraception).
  • Presence of generalized seizures, or reflex seizures i.e. triggered by a sensory stimulus.
  • Presence of a language or hearing impairment.
  • Non-English speakers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Eye position and tense arousal over time a metrics for sustained attention in conditioned fear.
After conditioning the conditioned stimulus induces autonomic metrics like skin conductance and cognitive ratings like expectancy of the unconditioned stimulus after conditioning. Activity across blocks in the conditioning stage demonstrates that the skin conductance can produce a progressive decrease in skin conductance over the conditioning stage of our fear conditioning protocol. The decline is not apparently related to habituation or changes in the skin conducting electrodes or recording system. It does correspond to the decrease in performance of a visual fixation task which is part of the fear conditioning during the conditioning stage; and to an increase in the unpleasant psychologic activation termed tense arousal over the same stage. If both these changes are found he then we may conclude that sustained task related attention is produced during fear conditioning
Behavioral: Skin conductance levels and slopes over time in conditioned fear as metrics.as metrics for anxiety
After fear conditioning the cue induces autonomic responses like skin conductance and cognitive ratings like expectancy of the unconditioned stimulus after cueing or conditioning. Activity across blocks in the conditioning stage shows that the skin conductance can be described by levels, and slopes which might be related to state anxiety and trait anxiety (Spielberger trait and state anxiety inventory or questionnaire). These skin conductance measures may be concrete metrics for psychological processes in healthy subjects. We will carry out a partial correlation analysis of levels, state anxiety and trait anxiety, and then a similar analysis of slopes, state anxiety and trait anxiety. These results may show that concrete skin conductance levels and slopes are related to metrics of subjective self report measures of state and trait anxiety.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Conditioned fear as assessed by skin conductance
Time Frame: 5 hours
Concrete metric is skin conductance measured in microSiemens.
5 hours
Anxiety as assessed by the Spielberg Anxiety Inventory
Time Frame: 5 hours
Higher scores on the Spielberg Anxiety Inventory indicates more anxiety.
5 hours
Experimental Pain as assessed by a pain rating scale
Time Frame: 5 hours
Pain Rating for Unpleasantness on a scale of 0 - 10 where 10 is the worst imaginable.
5 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Parts of the brain outside the predicted models.
Time Frame: The whole duration of the study up to 5 years
This outcome will be identified by the proportion of electrodes in parts of the brain outside the predicted models with both activation (ERSP) and interactions with other parts of the brain (ERC). If there is significance for both these measures in a part of the brain then it may be added to the network for expectation of pain.
The whole duration of the study up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

University of Maryland
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Fred A Lenz, MD PhD, Dept of Neurosurgery, Hopkins University.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Anticipated)

June 1, 2028

Study Completion (Anticipated)

October 1, 2029

Study Registration Dates

First Submitted

November 2, 2018

First Submitted That Met QC Criteria

November 8, 2018

First Posted (Actual)

November 14, 2018

Study Record Updates

Last Update Posted (Actual)

May 16, 2023

Last Update Submitted That Met QC Criteria

May 12, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA_00079932
  • 2R56NS038493-16A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The PI and Co-PIs are working with the Johns Hopkins Pain Research Institute to set up a website for the Institute to include the labs carrying out pain research in the Department of neurosurgery. As a part of this effort we will include the Functional Neurosurgery Lab to share the following information in the public domain: 1. Our research focus. 2. Biosketches of the investigators 3. All publications as final manuscripts at the time of acceptance for publication, 4. Funded grant applications 5. Collaborators 6. Contact information.

IPD Sharing Time Frame

The website will be complete in 3 years.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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